Introduction
Rheumatoid arthritis (RA) is one of the most prevalent chronic
autoimmune diseases, which involves the joints and even cause cartilage
and bone damage(1). Autoimmunity and inflammation play important role in
the pathogenesis of RA, however the precise mechanism is still
unclear(1).
Myeloid-derived suppressor cells (MDSC) are heterogeneous myeloid cell
populations that expand in tumors(2), infections (3), autoimmune
diseases(4), and other abnormal conditions. The term ‘myeloid-derived
suppressor cells’ was first coined in 2007, indicating its
characteristics of myeloid origin and immunosuppressive function(5).
MDSCs in mice express both CD11b and Gr-1 markers and have two
subgroups: polymorphonuclear MDSCs (PMN-MDSCs)
(CD11b+Ly6G+Ly6Clow)
and mononuclear MDSCs (M-MDSCs)
(CD11b+Ly6G-Ly6Chigh)(6). The role
of MDSC in RA pathogenesis is controversial due to their heterogeneity,
and some researchers hold the view that MDSCs are protective in RA(7, 8)
by inhibiting the proliferation of T cells and B cells, while others
believe they are proinflammatory(9, 10). PMN-MDSCs account for the
majority of MDSCs in collagen-induced arthritis (CIA), and studies have
found that PMN-MDSCs have a therapeutic impact in CIA mice(8, 11).
However, we found that PMN-MDSCs play a distinct role in CIA. Therefore,
we aimed to explore the mechanism underlying PMN-MDSC-mediated CIA.
The pivotal role of B cells in RA is clearly established by the presence
of disease-specific autoantibodies and efficacy of B cell-targeting
biological agents(12). A recent study showed that activated B cells also
produce cytokines as well as antibodies(12), and B cell-derived TNF
could control the development of autoantibodies and regulate the
severity of CIA, whereas T cell-derived TNF is dispensable during
arthritis(13). Qin et al(14) also found that age-associated B cells
induced the activation of fibroblast-like synoviocytes (FLS) via
TNF-𝛂,
which indicated the important role of TNF-𝛂+ B cells
in the pathogenesis of RA. Previous studies mainly focused on the
PMN-MDSC regulating T cells, less researches have been done on
regulating B cells, so we want to add something to this aspect.
Here, we first found that PMN-MDSCs were proinflammatory in CIA model,
which could facilitate TNF-𝛂 secretion and proliferation of B cells, and
inhibit apoptosis of B cells. Thus, our findings explained the
pathogenic role of PMN-MDSCs and its regulation of B cells in RA, which
provided a novel mechanism of RA.